Stramba-Badiale M, Pessano P, Kirchengast M, Schwartz P J
Instituto di Clinica Medica Generale e Terapia Medica, Università di Milano, Italy.
Am Heart J. 1995 Mar;129(3):549-56. doi: 10.1016/0002-8703(95)90284-8.
The ineffectiveness of traditional antiarrhythmic agents in preventing sudden cardiac death has increased the interest in drugs that prolong refractoriness. Ambasilide is a new potassium channel blocking agent that appears to prolong refractoriness at short and long cycle lengths. We assessed the effects of ambasilide, 5 mg/kg intravenous (i.v.) bolus plus 5 mg.kg-1.hr-1 i.v. infusion, in 16 anesthetized cats in which ventricular arrhythmias could be induced reproducibly by the combination of acute myocardial ischemia and increased sympathetic activity. Ambasilide decreased heart rate and blood pressure and prolonged QRS duration (26%, p < 0.05), QTc (17%, p < 0.0001), and JTc (16%, p < 0.005). Ambasilide also shifted the strength-interval curve for ventricular refractoriness by 17 to 22 msec to the right (p < 0.001). Ventricular fibrillation was observed in 7 animals and never occurred after ambasilide (p < 0.001); however, 4 (57%) of these cats had sustained ventricular tachycardia requiring cardiac massage. Ambasilide prevented nonsustained ventricular tachycardia in 2 (40%) of 5 animals. The antiarrhythmic effect of ambasilide persisted when heart rate was kept constant by atrial pacing. In no case was proarrhythmia observed. Ambasilide had a significant electrophysiologic effect at the ventricular level in the cat because it did prolong QTc and ventricular refractoriness. Therefore ambasilide showed an antifibrillatory effect but provided only a partial protection against lethal arrhythmias induced by acute myocardial ischemia and sympathetic activation.
传统抗心律失常药物在预防心源性猝死方面的无效性增加了人们对延长不应期药物的兴趣。氨巴利特是一种新型钾通道阻滞剂，似乎能在短周期和长周期长度下延长不应期。我们评估了氨巴利特（静脉推注5mg/kg加静脉输注5mg·kg-1·hr-1）对16只麻醉猫的影响，在这些猫中，急性心肌缺血和交感神经活动增加的联合作用可重复性地诱发室性心律失常。氨巴利特降低了心率和血压，延长了QRS时限（26%，p<0.05）、QTc（17%，p<0.0001）和JTc（16%，p<0.005）。氨巴利特还使心室不应期的强度-间期曲线向右移动了17至22毫秒（p<0.001）。7只动物出现了室颤，氨巴利特给药后从未发生室颤（p<0.001）；然而，这些猫中有4只（57%）发生了持续性室性心动过速，需要进行心脏按摩。氨巴利特在5只动物中的2只（40%）中预防了非持续性室性心动过速。当通过心房起搏使心率保持恒定时，氨巴利特的抗心律失常作用持续存在。在任何情况下均未观察到促心律失常作用。氨巴利特在猫的心室水平上具有显著的电生理作用，因为它确实延长了QTc和心室不应期。因此，氨巴利特显示出抗纤颤作用，但仅对急性心肌缺血和交感神经激活诱发的致死性心律失常提供了部分保护。
